Working Mechanisms of Ribbon Synapses in Cochlea

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Inner hair cells (IHCs) in the cochlea synapse with type I primary auditory neurons (spiral ganglion neurons, SGNs), providing the main information pathway to auditory brain. This synapse are characterized by their pre-synaptic ribbon structure, and therefore called ribbon synapses. It is known that the specific structure and molecular composition in the presynaptic compartment are responsible for the quick and long-lasting responses to sound. However, little detail is known how the ribbon synapses in cochlea play such roles. ***Ribbon synapses are mainly seen in both retina and cochlea, but the research of cochlear ribbon synapse is much behind of that in retina. Specifically, many proteins that are critical for synaptic transmission in conventional synapse are missing in IHCs ribbon synapse. Functional specificities remains to be explored for those proteins in cochlear ribbon synapses. ***Three aims will be achieved: (1) to explore the functional roles of two ribbon proteins: otoferlin and piccolino in the IHC synaptic transmission, (2) to verify whether there is a functional dissembling and reassembling of presynaptic ribbons in IHCs, and (3) to explore the molecular substrate for signal coding at ribbon synapses by verifying the structure and molecular changes in the repaired ribbon synapses after noise damage.***Otoferlin and piccolino will be down-regulated respectively. The impact of the down-regulation on morphology, and the coding function of auditory nerve fibers (ANFs) will be investigated in order to verify their roles and working mechanisms in synaptic transmission. ***To achieve the second aim, dynamic observation of ribbon synaptic structure will be performed using various morphological methods in combination with immunohistological method, molecular biology methods. Moreover, otoferline and picccolino knockout will be used to identify the potential roles of those two proteins in the assembly of ribbons. ***The third aim is based upon my recent progress on noise induced damage and repair around ribbon synapses. In this line of research, we demonstrated that coding deficits of auditory nerve was developed in association with synaptic repair after initial damage. This suggested a possibility that the repaired synapses may be different in their protein/structure composition. We will observe such difference caused by noise damage and repair with focus on ribbon side of the synapse. Various methods will be utilized for such changes and for the correlation between structure and function.***The long term goal of the research is to fully understand the working mechanism of ribbon synapses in the auditory sensorial organ in order to have better management of damage and repair in future.